Spina bifida or myelomeningocele (MM) is the most common permanently disabling condition in the U.S. and one of the most complex birth defects compatible with life. It is caused by failure of the spinal column to close completely during the first month of pregnancy, resulting in varying degrees of paralysis and weakness in the lower extremities. Osteoporosis and fractures are common problems in this population, most likely due to decreased ambulation and mechanical loading of the skeleton. A top priority for research in spina bifida is the identification of risk factors for osteoporosis and subsequent mitigation of these risk factors to prevent osteoporosis and osteoporotic fractures. Since adolescence is a critical period for bone acquisition in non-disabled children, it is hypothesized that bone mass may be maximized in children with MM by maintaining upright mobility (walking) as long as possible through adolescence. This study will identify risk factors for osteoporosis in MM, particularly risk factors related to ambulation and mechanical loading of the skeleton. The specific aims are (1) to examine longitudinal changes in bone density, size, and structural (strength) properties in children and adolescents with MM and to compare these changes with those in typically developing controls, (2) to identify potential risk factors for deficient bone acquisition and the development of osteoporosis, including level of neurological involvement, ambulatory status, gait characteristics, and amount of walking (steps per day), and (3) to explore whether maintaining ambulation (upright mobility) through adolescence is associated with significant gains in bone mass. To achieve these aims, children and adolescents with MM ages 6-13 years and controls of the same age will be assessed longitudinally over a 3-year follow-up period. Bone density, size, and strength will be measured in the tibia using computed tomography (CT) imaging. Gait characteristics will be measured through three-dimensional computerized gait analysis, and the amount of walking will be quantified with an activity monitor. To fully characterize the study subjects, other relevant information will also be obtained, including medical history, physical examination, Tanner stage of sexual development, skeletal age, dietary intake, and major determinants of bone formation. The bone properties will be related to the other measures to identify the most important risk factors for osteoporosis and to assess the importance of upright mobility (walking) in stimulating bone acquisition in children and adolescents with MM. PUBLIC HEALTH RELEVANCE Osteoporosis and fractures are common problems in persons with myelomeningocele (MM). This study will identify risk factors for osteoporosis in MM and explore whether osteoporosis can be prevented or lessened in severity by maintaining upright mobility (walking) as late as possible into adolescence. A slight delay in the transition to wheelchair mobility may make a large difference in osteoporosis prevention.